Preservatives In Cosmetic Products Research Articles

Amended Safety Assessment of Parabens as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 21 parabens as preservatives in cosmetic products. All of these ingredients are reported to function in cosmetics as preservatives; however, 5 are reported to also function as fragrance ingredients. The Panel reviewed relevant data relating to the safety of these ingredients under the reported conditions of use in cosmetic formulations. The Panel concluded that 20 of the 21 parabens included in this report are safe in cosmetics in the present practices of use and concentration described in this safety assessment when the sum of the total parabens in any given formulation does not exceed 0.8%. However, the available data are insufficient to support a conclusion of safety for benzylparaben in cosmetics.

Safety review of phenoxyethanol when used as a preservative in cosmetics.

Phenoxyethanol, or 2-phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram-negative and Gram-positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers - including children of all ages - when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200-fold higher) than those to which consumers are exposed when using phenoxyethanol-containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well-tolerated preservatives used in cosmetic products.

Human urine contamination with environmental pollutants: simultaneous determination using UPLC-MS/MS.

Paraben derivatives are widely used as an antifungal, antimicrobial preservative in cosmetic products, pharmaceuticals, and food. These molecules are called endocrine disruptors (EDCs). The exposure of the human body to paraben derivatives needs further study and for this purpose 200 urine samples were collected from Tunisian men and women aged between 5 and 90 years to determine three paraben derivatives: methylparaben (MP), ethylparaben (EP) and propylparaben (PP) using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The three major parabens were found in 95 urine samples. The obtained results indicate that MP, EP, and PP were detected in 57%, 46%, and 40% of all samples, respectively. Urinary concentration for the three parabens was in the range of 0.88-84.46 ng/mL, 0.52-29.2 ng/mL, and 0.51-28.17 ng/mL of PP, MP, and EP, respectively. In addition, the concentrations of the paraben derivatives in women were higher than those of men. These findings indicate that the exposure occurs from common products (foods, cosmetics, and pharmaceuticals). The Tunisian authorities should control the composition of packaging of these common products in order to protect humans against EDCs.

Development of a liquid chromatography/tandem mass spectrometry method for monitoring of long-term exposure to parabens.

Parabens, the alkyl esters of 4-hydroxybenzoic acid, are a family of compounds widely used as preservatives in cosmetic products, including for children, and some are permitted in foods. Parabens are known to be weak endocrine disruptors because they interfere with the function of endogenous hormones through binding to estrogen receptors. Therefore, the levels of parabens in biological samples indicate endocrine-disruptive exposure. In particular, hair samples can provide information on accumulated exposure to parabens. For monitoring of long-term exposure to parabens, an improved analytical method for rapid and direct determination in hair sample was developed involving ultra-performance liquid chromatography-tandem mass spectrometry using on-line extraction. Five parabens (methyl-, ethyl-, propyl-, butyl- and benzylparaben) were separated within 10 min after incubation with 1 N HCl. Parabens were separated using a Waters BEH C18 column (2.1 mm × 100 mm, 1.7 μm) and a mobile phase consisting of 10 mM ammonium acetate in water and acetonitrile with a gradient program at a flow rate of 300 μL/min. The analysis of the separated parabens was monitored with electrospray negative ionization tandem mass spectrometry. The linearity of the method was demonstrated by r2 ≥0.994. The limits of detection as defined by a signal-to-noise ratio of 3 were 1-5 ng/g. The mean concentration of the five parabens in hair of human subjects was measured to be 55.6 ± 24.3 to 136.9 ± 48.5 ng/g. The levels of parabens in hair samples may play an important role in understanding probable endocrine-disruptive exposure, and the described method could be used to evaluate and monitor long-term exposure to parabens as endocrine disruptors.

A Green and Rapid Analytical Method for the Determination of Hydroxyethoxyphenyl Butanone in Cosmetic Products by Liquid Chromatography

An analytical method for the determination of hydroxyethoxyphenyl butanone, which is used as an alternative preservative in cosmetic products, has been developed and validated for the first time. The method is based on a simple ultrasound-assisted lixiviation of the analyte from the cosmetic matrix followed by liquid chromatography with UV spectrophotometric detection. Under optimized conditions, the method limit of detection and limit of quantification values were 30 and 90 µg·g−1, respectively. The method was validated with good recovery values (86–103%) and precision values (RSD 0.2–4.7%). Finally, the proposed analytical method was successfully applied to 7 commercially available cosmetic samples including both lipophilic and hydrophilic matrices, such as moisturizing cream, sunscreen, shampoo, liquid hand soap, and make-up. Additionally, a laboratory-made cosmetic cream containing the target analyte was prepared and analyzed. The good analytical figures of merit of the proposed method, in addition to its environmentally-friendly characteristics, demonstrate its usefulness to perform the quality control of cosmetic products to ensure the safety of consumers.

Contact Allergy to Preservatives—Is the European Commission a Commendable Risk Manager?

Although preservatives are necessary to prevent deterioration by microbial growth in cosmetic products, daily skin contact with preserved cosmetic products may cause a preservative contact allergy. Only preservatives with sufficient pre-market risk assessment, presumably being safe for the consumer from a public health point of view, are permitted for use in cosmetic products in the European Union. Notwithstanding the efforts by the European Commission (EC) to avoid epidemics of contact allergy, the former epidemic of contact allergy to methyldibromo glutaronitrile and the unprecedented epidemic of contact allergy to methylisothiazolinone show the procrastination of the European Union risk management process for cosmetic ingredients. Timely risk management is of the utmost importance to avoid rapidly increasing numbers of contact allergy to turn into full-blown epidemics. It is therefore proposed that in order to avoid future epidemics of contact allergy to preservatives, the allowed preservatives in cosmetic products should be entered onto Annex V on a time-limited basis only, and they must be re-evaluated in order to stay on Annex V.

Determination of alternative preservatives in cosmetic products by chromophoric derivatization followed by vortex-assisted liquid–liquid semimicroextraction and liquid chromatography

An analytical method for the simultaneous determination of phenethyl alcohol, methylpropanediol, phenylpropanol, caprylyl glycol, and ethylhexylglycerin, which are used as alternative preservatives in cosmetic products, has been developed. The method is based on liquid chromatography with UV spectrophotometric detection after chromophoric derivatization with benzoyl chloride and vortex-assisted liquid–liquid semimicroextraction. Different chromatographic parameters, derivatization conditions, and sample preparation variables were studied. Under optimized conditions, the limits of detection values for the analytes ranged from 0.02 to 0.06µgmL−1. The method was validated with good recovery values (84–118%) and precision values (3.9–9.5%). It was successfully applied to 10 commercially available cosmetic samples. The good analytical features of the proposed method besides of its environmentally-friendly characteristics, make it useful to carry out the quality control of cosmetic products containing the target compounds as preservative agents.

On‐line Concentration and Separation of Parabens by Micellar Electrokinetic Chromatography Using Polymer Solutions

AbstractSimultaneous separation and quantification of seven parabens commonly used as preservatives in cosmetic products, by micellar electrokinetic chromatography with a stacking technique has been demonstrated. An effective on‐line concentration strategy involving a combination of sweeping and the use of polymer solutions is a key feature of the proposed method, which successfully determined individual parabens. The analysis parameters such as injection time, pH and concentration of phosphate solution, and concentration of sodium dodecyl sulphate (SDS) and poly(ethylene oxide) (PEO) were examined. The optimum conditions were found to be as follows: a 15 mM phosphate solution (pH 9.5) containing 20 mM SDS for filling the capillary, and for the separation electrolytes, 0.100% PEO (8 MDa) added to the phosphate and SDS solution of the same composition as for the capillary. The entire analysis process was completed in 13 min and a 930‐2200‐fold enhancement factor was achieved. The LODs (S/N = 3) for this approach were in the range from 4.32 to 7.78 nM. The linear range for each paraben was between 50 nM and 5.0 μM (R2 > 0.990). The optimized method was then successfully applied to the determination of parabens in commercial cosmetic products.

The Use of Preservatives in Cosmetic Products and Their Efficiency Testing

The Use of Preservatives in Cosmetic Products and Their Efficiency Testing

The cosmetic allergy conundrum: inference of an immunoregulatory response to cosmetic allergens

The ability to be sensitized to experimental contact allergens declines significantly with increasing age, from as early as age 40 years. In contrast, the rate of contact allergy to chemical allergens (haptens) in cosmetic products significantly increases with age. This has been explained previously on the basis of greater cumulative exposure in the older age groups. However, outbreaks of contact allergy to preservatives in cosmetic products recorded soon after their introduction to the market have also shown a significantly higher rate among older adult age groups. This association with increasing age cannot be readily explained by exposure history or pattern, and is not compatible with a sensitizing/stimulatory reaction that degrades with age as the sole immune response. From this, the existence of a second, tolerizing/regulatory arm to the immune response to cutaneous haptens that possibly becomes less effective with age at a higher rate than the sensitizing/stimulatory arm can be inferred. This reinforces the view that current clinical and experimental observations of allergic contact dermatitis are best explained by an immune system with the functional ability to produce both sensitizing/stimulatory and tolerizing/regulatory responses.

Medicago spp. extracts as promising ingredients for skin care products

Agro-industrial by-products have the potential to be used with different purposes thus providing economical advantage to otherwise disposable residues. In particular, the field of skin care products and cosmetics may benefit from these remaining materials. Hydro-alcoholic extracts of seven species of Medicago (M. minima, M. tornata, M. truncatula, M. rigidula, M. scutelata, M. segitalis and M. sativa) were screened for antioxidant, cytotoxicity and antimicrobial activities aiming at their application as functional ingredient in skin formulations. Antioxidant activity was evaluated by standard methods such as DPPH· and FRAP. In both methods the antioxidant activity of M. segitalis displayed the highest antioxidant activity (214.49±6.69μmol Trolox equivalent per g db for DPPH; 120.84±1.86μmol/mg db for FRAP). For DPPH M. rigidula showed the lowest antioxidant activity (127.18±1.96μmol Trolox equivalent per g db) and for FRAP M. minima showed the lowest one (58.05±6.09μmol per mg db). Also, the total phenolic and total flavonoid contents (TPC and TFC, respectively) were evaluated. The TPC of the different extracts varied from 21.96mg to 36.41mg GAE/g db sample, being the highest TPC obtained for M. minima and the lowest for the M. scutelata. TFC varied from 5.54 to 11.67mg CEQ/gdb sample. Linear negative correlations were established between the total phenol contents and for both the antioxidant activity methods. The extracts were also screened for cytotoxicity using MTS and LDH assays in two different skin cell lines (HaCaT and HFF-1) and showed low cytotoxicity. Preliminary assays for antimicrobial potential showed that extracts from Medicago display antibacterial activity, with MIC values of 31.3μg/mL and 125μg/mL for some Gram-positive and Gram-negative bacteria, respectively. Taken together, the results suggested that Medicago hydro-alcoholic extracts are a potential source of natural compounds with high levels of antioxidant activity, low cytotoxicity for skin cells and the ability to potentially prevent microbial infections of the skin due to its antimicrobial effect, as well as contribute as a natural preservative in cosmetic products. All referred above justify their possible uses in skin care products.

Development of a Quantitative Analytical Method for Determining the Concentration of Human Urinary Paraben by LC-MS/MS

Parabens, the esters of p-hydroxybenzoic acid, have been widely used as antimicrobial preservatives in cosmetic products, drugs, and processed foods and beverages. However, some parabens have been shown to have weak estrogenic effects through in vivo and in vitro studies. Because such widespread use has raised concerns about the potential human health risks associated with exposure to parabens, we developed a simultaneous analytical method to quantify 4 parabens (methyl, ethyl, propyl, and butyl) in human urine, by using solid-phase extraction and high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. This method showed good specificity, linearity (<TEX>$R^2$</TEX> > 0.999), accuracy (92.2-112.4%), precision (0.9-9.6%, CV), and recovery (95.7-102.0%). The LOQs for the 4 parabens were 1.0, 0.5, 0.2, and 0.5 ng/mL, respectively. This method could be used for quick and accurate analysis of a large number of human samples in epidemiological studies to assess the prevalence of human exposure to parabens.

Determination of seven preservatives in cosmetic products by micellar electrokinetic chromatography

A micellar electrokinetic chromatography method using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant, coupled with UV-Vis detection, was developed for the simultaneous determination of seven preservatives, including methyl-, ethyl-, propyl- and butyl-paraben and phenol, phenoxyethanol and resorcinol. The method involved optimizing the pH of the phosphate buffer and concentrations of CTAB, ethanol and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The preservatives were well separated using optimum conditions and separated within 10min at a separation voltage of -12.5 kV with the 1.0 mM phosphate buffer (pH 7.0) containing 90 mM CTAB, 25 mM HP-β-CD and 10% (v/v) ethanol. Satisfactory recoveries (84.1-103.0%), migration time (RSD < 3.1%) and peak area (RSD < 4.5%) repeatabilities were achieved. Detection limits of the preservatives were between 0.31 and 1.52μg mL(-1) (S/N=3, n=5). The optimized method was successfully applied to the simultaneous determination of these preservatives in 10 commercial cosmetic products.

Large volume sample stacking with EOF and sweeping in CE for determination of common preservatives in cosmetic products by chemometric experimental design

This study proposes a capillary electrophoresis method incorporating large volume sample stacking, EOF and sweeping for detection of common preservatives used in cosmetic products. The method was developed using chemometric experimental design (fractional factorial design and central composite design) to determine multiple separation variables by efficient steps. The samples were loaded by hydrodynamic injection (10 psi, 90 s), and separated by phosphate buffer (50 mM, pH 3) containing 30% methanol and 80 mM SDS at -20 kV. During method validation, calibration curves were found to be linear over a range of 5-100 μg/mL for butyl paraben and isobutyl paraben; 0.05-10 μg/mL for ethyl paraben; 0.2-50 μg/mL for dehydroacetic acid; 0.5-70 μg/mL for methyl paraben; 5-350 μg/mL for sorbic acid; 0.02-450 μg/mL for p-hydroxybenzoic acid and 0.05-10 μg/mL for salicylic acid and benzoic acid. The analytes were analysed simultaneously and their detection limits (S/N = 3) were down to 0.005-2 μg/mL. The analysis method was successfully used for detection of preservatives used in commercial cosmetics.

Simultaneous determination of 21 preservatives in cosmetics by ultra performance liquid chromatography

An ultra performance liquid chromatography (UPLC) method has been developed for the simultaneous determination of 21 preservatives: 2-methyl-4-isothiazoline-3-ketone, bronopol, 5-chloro-2-methyl-4-isothiazoline-3-ketone, benzyl alcohol, 2-phenoxyethanol, methyl-p-hydroxy benzoate, ethyl-p-hydroxy benzoate, methyl benzoate, 4-hydroxybenzoic acid iso-propyl ester, propyl-p-hydroxy benzoate, 4-chloro-3-methylphenol, ethyl benzoate, 2-phenylphenol, 4-hydroxybenzoic acid iso-butyl ester, butyl-p-hydroxy benzoate, 4-chloro-3,5-dimethylphenol, phenyl benzoate, 2,4-dichloro-3,5-dimethylphenol, 2-benzyl-4-chlorophenol, triclocarban and triclosan in cosmetics. A Waters ACQUITY UPLC BEH C(18) column was used with 0.1% formic acid solution as the mobile phase under the condition of gradient elution. Preservatives were extracted with methanol by ultrasonicator, and then they were analysed by UPLC-PDA detector. All these preservatives were baseline separated in 8.5 min. The pre-treatment method of samples and the chromatographic condition of analysis were critically examined in this study. The recoveries ranged from 90.5 to 97.8%, with RSD values below 3.2%, and all correlation coefficients (r) were no less than 0.9997. Thus, this method could be used for analysing the preservatives in cosmetic products.

Parabens as urinary biomarkers of exposure in humans.

BackgroundParabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure.ObjectivesAssessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid and excreted in the urine as conjugates. Still, monitoring urinary concentrations of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to parabens. p-Hydroxybenzoic acid is a nonspecific biomarker, and the varying estrogenic bioactivities of parabens require specific biomarkers. Therefore, we evaluated the use of free and conjugated parent parabens as new biomarkers for human exposure to these compounds.ResultsWe measured the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in a demographically diverse group of 100 anonymous adults. We detected methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most important, however, we found that parabens in urine appear predominantly in their conjugated forms.ConclusionsThe results, demonstrating the presence of urinary conjugates of parabens in humans, suggest that such conjugated parabens could be used as exposure biomarkers. Additionally, the fact that conjugates appear to be the main urinary products of parabens may be important for risk assessment.

Quantification of the urinary concentrations of parabens in humans by on-line solid phase extraction-high performance liquid chromatography–isotope dilution tandem mass spectrometry

Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as antimicrobial preservatives in cosmetic products, pharmaceuticals, and food processing. However, weak estrogenicity of some parabens has been revealed from several studies. Human exposure to parabens may be assessed by measuring the conjugated or free species of these compounds or their metabolites in urine. We have developed a method using on-line solid phase extraction-high performance liquid chromatography–isotope dilution tandem mass spectrometry with peak focusing to measure the urinary concentrations of methyl, ethyl, propyl, n- and iso- butyl, and benzyl parabens. This method has good reproducibility and accuracy with detection limits for all analytes below 0.2 ng/mL in 100 μL of urine, and permits quick and accurate analysis of a large number of samples in epidemiologic studies for assessing the prevalence of human exposure to parabens. Using this method, we detected methyl, ethyl, and propyl parabens, mostly as conjugated species, in 22 urine samples collected from anonymous adults.

Comparative study for the analysis of parabens by micellar electrokinetic capillary chromatography with and without large-volume sample stacking technique

The separation and determination of four parabens (methyl, ethyl, propyl, and butyl p-hydroxybenzoate) which are commonly used as preservatives in cosmetic products, by micellar electrokinetic capillary chromatography (MEKC) with and without large-volume sample stacking (LVSS) technique were compared. As an effective on-line concentration technique, LVSS was successfully combined with MEKC to determine neutral parabens in an acidic media. The effects of some typical parameters such as sample volume, buffer pH, temperature, and concentration of surfactant were examined. The detection limits for this LVSS-MEKC method were found to be 3.0 × 10 −7 M for each of the parabens based on the signal-to-noise ratio of 3, which were around 300 times lower than normal MEKC technique. The curves of peak response versus concentration were linear from 1.0 × 10 −6 to 5.0 × 10 −5 M with regression coefficients of 0.9987, 0.9960, 0.9925 and 0.9864, respectively. A simple and easy-manipulative sample preparation method was developed and validated by analyzing commercially available cosmetic samples. It was found that with current sample preparation process and instrumentation system, 0.5 g of sample is enough for the analysis of parabens preservatives in cosmetic product with satisfactory results.

Separation of Preservatives in Cosmetic Products by Micellar Electrokinetic Chromatography

This paper describes the methodological optimization and validation of a simple micellar electrokinetic chromatography for the rapid simultaneous separation of 2-methyl-4-isothiazolin-3-one, methylparaben, ethylparaben, propylparaben, and butylparaben. By using a 30 mM phosphate buffer (pH 7.2) containing 30 mM sodium dodecyl sulfate (SDS), an applied voltage of 10 kV and a separation temperature of 40 degrees C, a quantitative determination was achieved, resulting in an analysis time of approximately 4 min. Only dilution and filtration are needed before analysis. The parameters for validation, such as linear ranges, detection limits, accuracy, and precision, are also reported.

Formaldehyde allergy: A follow-up study

Background: Formaldehyde is a commonly used preservative in cosmetic products, cleaning agents and industrial products, and sensitization to formaldehyde frequently occurs. Objective: The aim of the study was to evaluate the effect of extensive information and exposure assessment of formaldehyde on the prognosis of eczema. Methods: The present study was designed as a clinical follow-up study of formaldehyde-sensitive patients. 105 patients diagnosed as formaldehyde allergic in the period January 1 1990 to December 31 1994 were thoroughly informed about their allergy, and exposure assessment was performed as a formaldehyde analysis on the patients' products. Results: At follow-up 1 to 5 years later, 57 patients accepted the invitation to attend the outpatient clinic for an interview and a skin examination by a dermatologist, and were also at this time asked to bring products to which they were currently exposed for formaldehyde analysis. Evaluated by reported number of eczema eruptions and from objective skin examination patients had generally improved from their first visit to the department. At follow-up, 38 of 49 patients bringing products for analysis were still exposed to formaldehyde, as assessed by formaldehyde analysis on their products. There was a trend that severe eczema was found more often in patients still exposed to formaldehyde, but this finding was not statistically significant. Thirty-seven patients reported that they “paid attention to their allergy” when buying and using cosmetics or consumer products. Conclusion: Patients who paid attention to their allergy had statistically significantly fewer eruptions than those who did not.